Background: The phenotype of SHOX aploinsufficiency is highly variable also in affected members of the same family with broad differences in severity of short stature, disproportion, presence of Madelung deformity.
Case presentation: We present a family with a new mutation of SHOX gene. A 2.3 years old girl, born at term from unrelated parents, came to our observation for short stature. Her height was −2.02 SDS, arm span was normal, sitting heigh/height was +1.3 SDS, she had cubitus valgus. Target height was −1.7 SDS; in particular her mothers height was −3.1SDS, sitting height/height +3.7SDS; cubitus valgus, Madelung deformity and mesomelia were present. SHOX gene analysis, performed on the basis of mothers phenotype, revealed an heterozygous nonsense mutation (c.382C>T p. Gln 128Ter) both in the proband and in her mother. The same mutation was found in other four related adults and three children: the grandmothers height was −3.9 SDS with normal proportions; an uncle had Madelung deformity, mesomelia, height −3.1 SDS, sitting height/height +2.97 SDS; a cousin of the mother of our proband had stature −2.5 SDS, sitting height/height +3.7SDS; another cousin of the mother of our proband had a stature −1.58 SDS, normal proportions, bilateral bowing of tibia. As to children, mutation was identified in: a 4 years old boy with height −1.46SDS, sitting height/height +3.5SDS; a 8 years old girl with height −2.04 SDS, sitting height/height +3.5SDS; a 14 years old girl with Madelung deformity, stature −2.08 SDS, sitting height/height +2.7 SDS.
Conclusion: In preschool age SHOX defect related phenotype can be silent and a careful clinical evaluation of parents is useful for diagnosis. In our family clinical expression of SHOX aploinsufficiency is highly variable but almost all affected patients show increased sitting height/height. This confirms the usefulness of sitting height/height ratio, expressed in SDS for age and sex, as an index of suspicion of SHOX aploinsufficiency.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology